Birch Pollen Honey for Birch Pollen Allergy

Original Paper
Int Arch Allergy Immunol 2011;155:160–166
DOI: 10.1159/000319821
Received: March 8, 2010
Accepted after revision: July 21, 2010
Published online: December 23, 2010
Birch Pollen Honey for Birch Pollen
Allergy – A Randomized Controlled
Pilot Study
K. Saarinen a J. Jantunen a T. Haahtela b a
South Karelia Allergy and Environment Institute, Lappeenranta, and b Department of Allergy,
Helsinki University Central Hospital, Helsinki, Finland
Key Words
Birch pollen ⴢ Complementary medicine ⴢ Honey ⴢ Rhinitis
Abstract
Background: Only a few randomized controlled trials have
been carried out to evaluate various complementary treatments for allergic disorders. This study assessed the effects
of the preseasonal use of birch pollen honey (BPH; birch pollen added to honey) or regular honey (RH) on symptoms and
medication during birch pollen season. Methods: Forty-four
patients (59% female, mean age 33 years) with physiciandiagnosed birch pollen allergy consumed either BPH or RH
daily in incremental amounts from November 2008 to March
2009. Seventeen patients (53% female, mean age 36 years)
on their usual allergy medication served as the control
group. From April to May, patients recorded daily rhinoconjunctival and other symptoms and their use of medication.
Fifty patients completed the study. Results: During birch
pollen season in 2009, BPH patients reported a 60% lower
total symptom score (p ! 0.01), twice as many asymptomatic
days (p ! 0.01), and 70% fewer days with severe symptoms
(p ! 0.001), and they used 50% less antihistamines (p ! 0.001)
compared to the control group. The differences between the
BPH and RH groups were not significant. However, the BPH
patients used less antihistamines than did the RH patients
(p ! 0.05). Conclusions: Patients who preseasonally used
© 2010 S. Karger AG, Basel
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BPH had significantly better control of their symptoms than
did those on conventional medication only, and they had
marginally better control compared to those on RH. The results should be regarded as preliminary, but they indicate
that BPH could serve as a complementary therapy for birch
pollen allergy.
Copyright © 2010 S. Karger AG, Basel
Introduction
Complementary and alternative medicine (CAM), including therapeutic and diagnostic approaches different
from conventional medicine such as homeopathy and
antioxidant therapy, is widely used for allergic disorders
[1, 2]. In the treatment of seasonal (intermittent) rhinitis
some dietary supplements such as butterbur (a plant, i.e.
Petasites hybridus) and vitamin C have been associated
with some beneficial effects, but most products lack supporting clinical evidence [3–5]. A few other therapies, including spirulina (blue-green algae), acupuncture, and
phototherapy, also hold some promise [6, 7] but have not
been integrated into the general treatment of allergic rhinitis. Given the high prevalence of allergic diseases and
the associated costs of CAM treatments, Resnick et al. [5]
concluded that the efficacy of CAM modalities should be
challenged with randomized placebo-controlled trials in
Correspondence to: Dr. Kimmo Saarinen
South Karelia Allergy and Environment Institute
Lääkäritie 15
FI–55330 Tiuruniemi (Finland)
Tel. +358 5 432 8333, Fax +358 5 432 8625, E-Mail all.env @ inst.inet.fi
order to establish appropriate guidelines for the use of
CAM.
Wild honey, which has a variety of positive nutritional and health effects, is taken as an alternative medicine
for the treatment of gastrointestinal diseases, coronary
artery disease, and infected wounds [8–10]. Honey and
other bee products have antibacterial activity [11]. Even
antibiotic-resistant strains such as methicillin-resistant
Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have been shown to be as sensitive to honey as the antibiotic-sensitive strains of the
same species [12]. Phenolic acids and flavonoids have
been claimed to be the main cause of the protective effect [13]. Microbes form an integral part of honey, but
most of them are in an inactive form due to the hygroscopicity, hyperosmolarity, acidity, peroxide content,
and antibiotic activities of honey [11]. The primary
sources of the microbial community present in honey
seem to be pollen and the microflora of the honeybee’s
digestive tract [14].
According to animal studies, daily oral administration of bee-collected pollen causes an antiallergic action
by reducing the cutaneous mast cell activation elicited by
IgE and specific antigens [15, 16]. On the other hand, honey consists of both proteins derived from secretions of the
pharyngeal and salivary glands of honeybee heads and
pollen which can cause allergic reactions to honey [17].
Among patients with allergic rhinoconjunctivitis, Rajan
et al. [18] compared the effects of unpasteurized honey,
pasteurized honey, and corn syrup with synthetic honey
flavoring ingested daily during pollen season. The members of neither honey group experienced relief from their
symptoms in excess of that seen in the placebo group.
There is little clinical evidence that honey has some value
in the control of allergic symptoms, yet this is a common
belief in folk medicine.
We assessed the effects of the preseasonal use of honey
in patients with allergic symptoms during birch pollen
season. In Finland, birch pollinosis afflicts 10–15% of
people and is often accompanied by cross-reactions to
various food substances [19].
Material and Methods
Honey Products
Two types of honey were used: locally collected, unpasteurized, and unfiltered organic honey, i.e. regular honey (RH), and
the same honey enriched with bee-collected pollen, i.e. birch pollen honey (BPH). Both products were produced and provided by
Kyösti Pitkänen in Kerimäki, SE Finland. Based on microscopical
Honey and Birch Pollen Allergy
counting, BPH contained 8,400 birch pollen grains and 50 alder
pollen grains per gram of honey, on average. RH did not contain
birch or alder pollen. The total pollen amounts were considerably
higher: 250,000 grains in BPH and 400 grains per gram in RH,
mostly due to dominant willows (Salix) being the main sources of
nectar and pollen for honeybees in the early season.
Patient Recruitment
Members of the local Allergy and Asthma Society were targeted by a newspaper advertisement, resulting in 110 responses.
The responders were interviewed in detail by telephone to confirm their physician-diagnosed birch pollen allergy. Sixty-one
volunteers were recruited. In 72% of the subjects, the diagnosis
was based on a positive skin prick test to birch pollen in addition
to typical symptom history. No further testing was performed
during the recruitment period. Asthma was not regarded as an
exclusion criterion. Informed consent was obtained from all of the
subjects in conjunction with the personal delivery of honey. Those
in the control group returned their consent by mail.
Study Design
A single-blind randomized trial was performed. A doubleblind study design was not applicable due to constraints in the
manufacturing and pollen analysis of BPH. Subjects were assigned to 3 groups: BPH, RH, and control. By the end of October
2008, all subjects in the first 2 groups had received 900 g of honey in similar containers without labels. The 2 types of honey
(BPH and RH) were indistinguishable in appearance or taste.
Each subject was instructed to consume honey on a daily basis,
starting with a small droplet (!1 g) in November and increasing
the intake at intervals of 3 weeks to a daily maximum of 1 teaspoon (approximately 8 g) till the end of March. The honey had
to be taken ‘as is’ so that it could dissolve slowly in the mouth.
Incorporating honey in tea or other substances was not permitted. The participants used diaries to record both the dosage and
possible allergy symptoms each day. Treatment compliance was
checked from the diaries. Subjects in the control group were advised not to take any honey products during the course of the
study.
After the honey regimen all subjects were given a new symptom diary for April and May, accompanied by 2 questionnaires.
The first questionnaire was about using honey during the preseason, its useful effects, and its adverse events. The patients filled
in a second questionnaire in June after birch pollen season and
rated their symptoms and the need for medication.
The main outcomes were the symptoms and the use of medication (antihistamine tablets, nasal sprays, or eye drops) recorded
daily in the diary. The study subjects graded 3 groups of symptoms: (1) conjunctival symptoms (itchy, swollen, watery, or sore
eyes), (2) nasal symptoms (sneezing, runny, itchy, or blocked
nose), and (3) other symptoms, such as itchy skin, from 0 (no
symptoms) to 3 (severe symptoms). Daily pollen concentrations
were measured by the South Karelia Allergy and Environment
Institute in Lappeenranta, SE Finland. Most of the study subjects
(85%) lived within a radius of less than 50 km from the pollenmonitoring site.
Data Analysis
The 3 study groups were compared with respect to symptomfree days (no need for medication), days with mild-to-moderate
Int Arch Allergy Immunol 2011;155:160–166
161
Table 1. Baseline characteristics of the 61 study patients
Subjects, n
Sex ratio (male/female)
Dropouts, n
Age, years 1
Asthma (physician-diagnosed), %
Birch pollen allergy
Duration, years1
Discomfort (0–10)1
Other allergies (physician-diagnosed), %
Oral allergy syndrome
Grass pollen
Cat or dog
Use of allergy medication, %
Year round
Regularly during pollen season
As needed during pollen season
1
RH
Control
25
12/13
5
33.0 (17.4)
8
19
6/13
3
32.9 (14.8)
11
17
8/9
3
35.6 (15.0)
0
22.7 (10.9)
6.6 (2.0)
18.6 (9.0)
7.3 (2.2)
18.4 (11.0)
6.8 (1.7)
65
25
35
81
44
56
43
43
36
5
75
20
18
69
13
7
86
7
Means with standard deviations.
symptoms, and days with severe symptoms using a 1-way analysis
of variance. Multiple comparison procedures were used to isolate
pairwise the mean differences in those cases where statistically
significant results were obtained. A day with severe symptoms
was defined as a day in which the sum of eye, nasal, and other
symptoms exceeded the value 3. Comparisons were also performed separately for conjunctival symptoms, nasal symptoms,
other symptoms, and total symptom scores, i.e. the sum of all
symptoms over the 2-month period. The frequencies of days with
medication were likewise compared.
Results
Pollen Season
The study season for birch pollination was the longterm average in terms of the total pollen count. The sums
of the daily concentrations were 27,460 in 2009 compared
to 29,700 which was the mean for 2002–2008. The number of days with high concentrations was 23 compared to
18 (the daily average exceeding 100 pollen grains per cubic meter), and the total number of days with birch pollen
in the air was 51 compared to 57. Birch pollen season
started on April 25 and high concentrations were measured up to May 26. Pollination of the closely related alder
was rather late (from April 2 to May 14, peaking on April
26), and the total concentration remained 30% lower than
the average (2,950 in 2009 compared to 4,270 for 2002–
2008).
162
BPH
Int Arch Allergy Immunol 2011;155:160–166
Study Subjects
The 61 subjects (35 females and 26 males) ranged from
8 to 79 years of age (mean 34.2) (table 1). Four patients also
reported asthma. The subjects had a long history of birch
pollen allergy (mean 20 years) and they rated the severity
of their symptoms, on average, at 6.8 on a scale from 0 to
10. All patients had suffered from nasal symptoms, 96%
from conjunctival symptoms, and 58% from other symptoms. Ninety-two percent of the patients reported daily
symptoms during pollen season, and all patients had used
antihistamine medication, usually on a regular basis during the season. Nasal sprays were used by 22 study subjects
(topical corticosteroids in 77%): 7/8 in the BPH group, 4/5
in the RH group, and 6/9 in the control group.
Fifty subjects completed the study and 11 dropped out.
Two patients did not like the sweetness of the honey, 1 had
pronounced itching in the mouth (BPH group), 1 experienced a worsening of atopic eczema (RH group), and 7
had undefined personal reasons.
Effect of Honey on Birch Pollen Allergy
During the 5 preseasonal months (November to
March), BPH was consumed on 117 days and RH on 127
days, on average. The total consumption of honey was a
rather constant 700 g per participant in both honey
groups. In the BPH group this corresponded to approximately 1.2 g of pollen (0.04 g of birch) ingested prior to
pollen season. A strong correlation between the reported
Saarinen /Jantunen /Haahtela
Table 2. Number of days in relation to allergic symptoms and use of medication during the birch pollen season
from April to May 2009 (61 days)
Symptom-free days
Mild-to-moderate symptoms
Severe symptoms
Conjunctival symptoms
Nasal symptoms
Other symptoms
Antihistamine tablets
Nasal sprays
Eye drops
BPH
RH
Control
p
32.1814.2a
20.5811.3
8.4810.8a
17.3816.2a
23.0812.9a
6.5811.2a
19.3815.7a
8.0813.5
6.9813.4
26.6816.5a
17.2811.2
17.2815.8a, b
19.5817.6a
29.8820.5a
15.2815.3a, b
32.3818.4b
13.4823.4
10.9819.7
14.1812.6b
18.4815.0
28.6820.9b
35.5821.6b
44.2812.3b
22.7820.8b
43.3820.0b
19.5822.0
6.0811.0
0.004
0.721
0.003
0.016
0.001
0.016
0.001
0.247
0.623
Va lues are presented as means 8 SD. Different superscript letters indicate significant differences between
the 3 groups in a pairwise post hoc Duncan test.
amount of honey consumed and the number of consumption days (Spearman’s rank correlation, ␳ = 0.581; p !
0.001) indicated good treatment compliance.
Subjects who took BPH had a significantly lower total
symptom score during pollen season in comparison to
the control group (fig. 1). The difference remained significant when analyzed separately for both April and
May. Differences between the 2 honey groups were not
statistically significant.
Subjects with either honey treatment had more asymptomatic days than did those in the control group (table 2).
The difference was more significant for the BPH group
(p ! 0.01) than for the RH group (p ! 0.05). Days with
mild-to-moderate symptoms were manifested rather
equally in all 3 groups, but severe symptoms were reported significantly less in the BPH group compared to the
control group (p ! 0.001), especially during the late pollen
season (fig. 2). Conjunctival and nasal symptoms were
less frequent in both honey groups compared to the control subjects, but differences between the BPH and RH
regimens remained nonsignificant.
During pollen season, patients using BPH needed significantly less antihistamine medication than did the
control subjects (p ! 0.001). The difference was also significant between the BPH and RH groups (p ! 0.05) but
not between the RH and control groups.
In addition to the effects on birch pollen allergy, favorable comments were made by 45% of the BPH group and
38% of the RH group. Specifically, fewer common colds
and stomach upsets and better general health were reported by 35% of the patients in the BPH group and by
38% in the RH group compared to 7% in the control
group.
‘Too sweet’ or ‘did not like the taste’ were the commonest reasons for any negative comments, these coming
from 35% of the BPH group and 44% of the RH group.
Adverse events, mostly mild itching in the mouth or skin
or a runny nose, were coincidentally recorded at the beginning of the regimen or following the dosing increase.
No severe systemic adverse events were reported.
Honey and Birch Pollen Allergy
Int Arch Allergy Immunol 2011;155:160–166
Total symptom score
210
In April
In May
p < 0.01
NS
180
150
NS
120
90
60
30
0
BPH
RH
Control
Fig. 1. Total scores of conjunctival, nasal, and other symptoms
over the 2-month period. The sums of daily values (0–3) in April
and May are presented as subject-specific averages with standard
errors in the 3 study groups. The difference between the BPH
group and the control group was significant in April (p ! 0.05)
and in May (p ! 0.05). NS = Not significant.
163
Pollen concentration
BPH
RH
Control
100%
50%
100
25%
0%
Discussion
As birches are the major deciduous trees in northern
Europe producing allergenic pollen [20], full avoidance is
not possible during pollen season. More than half a million people are allergic to birch pollen in Finland. In the
present study, the total symptom scores and severe symptoms correlated well with the daily pollen concentrations
in ambient air, as expected [21].
This was a preliminary study of the combined effects
of plain organic honey and bee-collected pollen, both of
interest in the treatment of allergic disorders. The patients used the study preparation preseasonally, which
may not be optimal. BPH is also difficult to standardize,
and the result is only valid for the particular honey used.
Clinical criteria were used to evaluate the outcome. Immunological tests could have provided additional information.
Traditionally, pollen allergic patients have been instructed to be wary of honey, or to avoid it altogether, as
honey often contains traces of compositae pollen in particular [22]. The clinical outcome was contrary to our expectations. The preseasonal use of BPH benefited most
subjects. In comparison to the control group, BPH doubled the number of asymptomatic days, reduced the
number of severe-symptom days by 70%, lowered the total symptom scores by 60 %, and halved the need for antihistamine medication. The differences between the 2
honey regimens (BPH and RH) were mostly nonsignificant, yet all the outcomes favored BPH. For example, in
the BPH group mild symptoms dominated, whereas in
164
Int Arch Allergy Immunol 2011;155:160–166
May 31
May 28
May 25
May 22
May 19
May 16
May 13
May 7
May 10
May 4
May 1
April 28
April 25
April 22
April 19
April 16
April 13
April 7
April 10
1
April 4
Fig. 2. Proportion of subjects with severe
symptoms (symptom score 13) in the 3
study groups over the course of the pollen
season from April to May 2009. The bars
indicate daily concentrations of alder and
birch pollen combined.
75%
April 1
Daily pollen concentration
(pollen grains per m3)
10,000
the RH group symptomatic days were evenly distributed
among mild, moderate, and severe symptoms. Alleviation of the more severe symptoms probably explained the
significant decrease in the need for antihistamines following the use of BPH.
After pollen season, 65% of the BPH group and 38% of
the RH group were in favor of the honey regimen in general. Two thirds of the subjects (65%) who took BPH reported less of a need for medication than during an average season before treatment. This was true for 44% of
those taking RH and for 36% of the control subjects.
BPH contained about 600 times more pollen than did
RH. A daily maximum dose of 1 teaspoon contained
some 2 million pollen grains, the majority of which were
willows (92%), together with approximately 67,000 birch
pollen grains (3.4%). This corresponds to temporal concentrations in the ambient air during the peak flowering
period in May. Despite the considerable number of pollen
grains, immunospot analysis of the allergenicity of BPH
resulted only in weak binding to the IgE in a laboratory
serum pool of birch-pollen-allergic patients (other than
the study subjects) [Mäkinen-Kiljunen, pers. comm. 23].
It is possible that enzymatic and microbial components
in honey have an effect on pollen proteins, reducing their
allergenic properties, but this hypothesis needs to be tested. RH showed no binding.
The benefit of BPH might be explained by a specific
immunotolerance developed during oral use of birch pollen in the complex honey vehicle [14]. BPH may have an
effect on specific and innate immunity at the same time
[24]. This suggestion certainly warrants further studies
Saarinen /Jantunen /Haahtela
but may provide new insight for the development of effective immunotherapy.
Regular organic honey, manufactured and stored below +28 ° C, also seemed to have some positive effects as
indicated by significant differences between the patients
on RH and the controls. This may be a placebo effect, but
a true benefit cannot be excluded. It should be emphasized that the organic honey used in the study was a prime
product based on carefully selected bee communities and
hives. It did include a range of pollens, albeit not birch
pollen.
Specific immunotherapy administrated via the sublingual (SLIT) or subcutaneous route is currently the only
therapy modifying or downregulating the allergic immune response [25]. Gradually increasing amounts of allergen are taken as drops, by oral spray, or as sublingual
tablets. Clinical use of SLIT is on the increase as evidence
has accumulated showing its efficacy and safety [26–29].
SLIT may even prevent new sensitizations and reduce the
risk of developing asthma, and its clinical efficacy lasts
several years [27, 30].
Boukraa and Sulaiman [12] state that when using any
hive product for medical purposes the challenging problems are dosage and safety. Participants in the present
study took BPH daily in incremental amounts, kept the
honey in the mouth for several minutes, rubbed it against
the palate with the tongue, and then swallowed. This
practice may have reduced adverse effects. If the allergenic preparation is swallowed immediately with water,
it may cause gastrointestinal side effects [27]. Altogether,
honey treatment was well tolerated with few expected local adverse effects. Patients adhered to the regimen and
89% of them wanted to participate in a follow-up study.
A new national allergy program for 2008–2018 has
taken off in Finland endorsing tolerance rather than allergen avoidance [31, 32]. More emphasis is placed on specific immunotherapy and the development of practical
and safe immunotherapies. Substantial evidence shows
that the balance between allergy and tolerance is dependent on regulatory T cells. Especially in early life, an environment rich in microbes reduces the subsequent risk
of allergic diseases [32, 33]. As reviewed by von Hertzen
et al. [32], continuous stimulation of the immune system
by environmental saprophytes via the skin, respiratory
tract, and gut appears to be necessary for the activation
of the regulatory network, including regulatory T cells
and dendritic cells. Exposure to microbial antigens, as
well as allergens in foodstuffs and the environment, is
decisive. Tolerance induced by allergen-specific regulatory T cells appears to be the normal immunological re-
sponse to allergens in nonatopic healthy individuals.
Healthy subjects have an intact functional regulatory T
cell response which is impaired in allergic subjects. Restoration of this response and tolerance induction has
been demonstrated during specific immunotherapy and
is crucial for a good therapeutic outcome. Honey with
pollen together with microbial elements might strengthen both unspecific and specific tolerance and serve as an
easy, cheap, and safe therapeutic option against various
pollen allergies.
Lots of questions remain. What would be an effective
and safe amount and formulation of pollen in honey?
What is the best way to administer honey to patients?
Which are the allergy-modifying elements in honey: microbes, enzymes, sugars, or proteins, and what are their
interactions? What are the mechanisms of the effects on
acquired or innate immunity? There now seems to be
some foundation for seeking the answers to such questions.
Honey and Birch Pollen Allergy
Int Arch Allergy Immunol 2011;155:160–166
Acknowledgements
This study was carried out at the South Karelia Allergy and
Environment Institute, which is a research unit of the Allergy and
Asthma Federation (a nongovernmental patient organization) in
Finland. We thank Kyösti Pitkänen for providing the impetus for
this trial and for supplying the honey products. The Institute’s
secretary Seija Pohjalainen assisted with the practical arrangements.
References
1 Bielory L, Lupoli K: Herbal interventions in
asthma and allergy. J Asthma 1999;36:1–65.
2 Ziment I, Tashkin DP: Alternative medicine
for allergy and asthma. J Allergy Clin Immunol 2000;106:603–614.
3 Guo R, Pittler MH, Ernst E: Herbal medicines for the treatment of allergic rhinitis: a
systematic review. Ann Allergy Asthma Immunol 2007;99:483–495.
4 Moyad MA: Conventional, complementary,
and alternative options for seasonal allergies. Urol Nurs 2008;28:227–228.
5 Resnick ES, Bielory BP, Bielory L: Complementary therapy in allergic rhinitis. Curr Allergy Asthma Rep 2008;8:118–125.
6 Xue CC, Li CG, Hugel HM, Story DF: Does
acupuncture or Chinese herbal medicine
have a role in the treatment of allergic rhinitis? Curr Opin Allergy Clin Immunol 2006;
6:175–179.
7 Man LX: Complementary and alternative
medicine for allergic rhinitis. Curr Opin
Otolaryngol Head Neck Surg 2009; 17: 226–
231.
165
8 Khan FR, Ul Abadin Z, Rauf N: Honey: nutritional and medicinal value. Int J Clin Pract
2007;61:1705–1707.
9 Alvarez-Suarez JM, Tulipani S, Romandini
S, Bertoli E, Battino M: Contribution of honey in nutrition and human health: a review.
Mediterr J Nutr Metab 2009, DOI: 10.1007/
s12349-009-0051-6.
10 Bogdanov S, Jurendic T, Sieber R, Gallmann
P: Honey for nutrition and health: a review. J
Am Coll Nutr 2008;27:677–689.
11 Olaitan PB, Adeleke OE, Ola IO: Honey: a
reservoir for microorganisms and an inhibitory agent for microbes. Afr Health Sci 2007;
7:159–165.
12 Boukraa L, Sulaiman SA: Rediscovering the
antibiotics of the hive. Recent Pat Antiinfect
Drug Discov 2009;4:206–213.
13 Beretta G, Orioli M, Facino RM: Antioxidant
and radical scavenging activity of honey in
endothelial cell cultures (EA.hy926). Planta
Med 2007;73:1182–1189.
14 Kacániová M, Pavlicová S, Hascík P, Kociubinski G, Knazovická V, Sudzina M,
Sudzinova J, Fikselova M: Microbial communities in bees, pollen and honey from Slovakia. Acta Microbiol Immunol Hung 2009;
56:285–295.
15 Ishikawa Y, Tokura T, Nakano N, Hara M,
Niyonsaba F, Ushio H, Yamamoto Y, Tadokoro T, Okumura K, Ogawa H: Inhibitory effect of honeybee-collected pollen on mast
cell degranulation in vivo and in vitro. J Med
Food 2008;11:14–20.
16 Ishikawa Y, Tokura T, Ushio H, Niyonsaba F,
Yamamoto Y, Tadokoro T, Ogawa H, Okumura K: Lipid-soluble components of honeybee-collected pollen exert antiallergic effect
by inhibiting IgE-mediated mast cell activation in vivo. Phytother Res 2009; 23: 1581–
1586.
166
17 Bauer L, Kohlich A, Hirschwehr R, Siemann
U, Ebner H, Scheiner O, Kraft D, Ebner C:
Food allergy to honey: pollen or bee products? Characterization of allergenic proteins
in honey by means of immunoblotting. J Allergy Clin Immunol 1996;97:65–73.
18 Rajan TV, Tennen H, Lindquist RL, Cohen L,
Clive J: Effect of ingestion of honey on symptoms of rhinoconjunctivitis. Ann Allergy
Asthma Immunol 2002;88:198–203.
19 Haahtela T, Hannuksela M, Mäkelä M, Terho
EO (eds): Allergia (in Finnish). Helsinki,
Kustannus Oy Duodecim, 2007.
20 Eriksson NE, Holmen A: Skin prick test with
standardized extracts of inhalant allergens
in 7,099 adult patients with asthma or rhinitis: cross-sensitizations and relationships to
age, sex, month of birth and year of testing. J
Investig Allergol Clin Immunol 1996; 6: 36–
46.
21 van Cauwenberg P, Bachert C, Passalacqua
G, Bousquet J, Canonica GW, Durham SR, et
al: Consensus statement on the treatment of
allergic rhinitis. Allergy 2000;55:116–134.
22 Kiistala R, Hannuksela M, Mäkinen-Kiljunen S, Niinimäki A, Haahtela T: Honey allergy is rare in patients sensitive to pollens:
European Academy of Allergology and Clinical Immunology. Allergy 1995; 50:844–847.
23 Mäkinen-Kiljunen S: Banana allergy in patients with an immediate-type hypersensitivity to latex: characterization of cross-reacting antibodies and allergens. J Allergy
Clin Immunol 1994;93:990–996.
24 Hammad H, Chieppa M, Perros F, Willart
MA, Germain RN, Lambrecht BN: House
dust mite allergen induces asthma via Tolllike receptor 4 triggering of airway structural cells. Nat Med 2009;15:410–416.
Int Arch Allergy Immunol 2011;155:160–166
25 Bousquet J, Lockey R, Malling H: Allergen
immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558–562.
26 Wilson DR, Torres-Lima I, Durham SR:
Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2003;
2:CD002893.
27 Passalacqua G, Guerra L, Pasquali M, Canonica GW: Non-injection routes for allergen immunotherapy: focus on sublingual
immunotherapy. Inflamm Allergy Drug
Targets 2006;5:43–51.
28 Potter PC: Update on sublingual immunotherapy. Ann Allergy Asthma Immunol
2006;96(suppl 1):S22–S25.
29 Kuo CH, Wang WL, Chu YT, Lee MS, Hung
CH: Sublingual immunotherapy in children:
an updated review. Pediatr Neonatol 2009;
50:44–49.
30 Serra HM, Alignani DO, Passalacqua G, Canonica GW, Correa SG: What do we need to
learn to optimize the SLIT alternative? Eur
Ann Allergy Clin Immunol 2006; 38: 158–
165.
31 Haahtela T, von Hertzen L, Mäkelä M, Hannuksela M, Allergy Programme Working
Group: Finnish Allergy Programme 2008–
2018 – time to act and change the course. Allergy 2008;63:634–645.
32 von Hertzen LC, Savolainen J, Hannuksela
M, Klaukka T, Lauerma A, Mäkelä MJ, et al:
Scientific rationale for the Finnish Allergy
Programme 2008–2018: emphasis on prevention and endorsing tolerance. Allergy
2009;64:678–701.
33 von Hertzen LC, Haahtela T: Disconnection
of man and the soil – reason for the asthma
and atopy epidemic? J Allergy Clin Immunol
2006;117:334–344.
Saarinen /Jantunen /Haahtela
`